It is known that nitroglycerin is pharmaceutically useful in the treatment or prevention of angina pectoris, myocardial infarction paroxysm, and cardiac insufficiency.
Among internal treatments for ischemic heart disease is vasodilator therapy in which nitroglycerin is used as a coronary vasodilator. Its effects include dilation of the coronary artery, releasing contraction of the coronary artery and dilation of collateral and resistance vessels thereby increasing the oxygen supply to the ischemic area of cardiac muscle. It is also known that nitroglycerin has effects such as dilation of arteries and reduction of blood pressure throughout the body (thereby reducing the load applied to the heart), dilation a sublingual tablet or as an ointment.
Sublingual tablets are generally used for the treatment of paroxysm due to angina pectoris but the duration of effectiveness is rather short, for instance 20 to 30 minutes.
When prolongeday be up to four to eight hours.
The ointment is generaly applied using a scaled parchment paper applicator which may be for instance 6 cm.times.9 cm in size. The amount of ointment applied is generally the maximum that can be tolerated without the onset of headache, this being a symptom of undesirable side effects. For instance 0.35 g ointment (containing 7.5 mg nitroglycerin) may be applied to the frontal chest skin and further amounts of 0.35 g until headache develops which shows the amount is then too great. Generally, the amount is from 0.7 to 1.5 g (containing 14 to 30 mg nitroglycerin) and the ointment is generally applied over 200 cm.sup.2 or more of the frontal chest skin.
To prevent evaporation of nitroglycerin and to prevent staining of clothes, the ointment is generally covered with a plastic film fixed to the skin by adhesive tapes.
The administration of ointment is thus rather inconvenient. It is difficult to determine the exact amount to be applied, and its application and removal can be messy.
Recently, three one-a-day type transdermal nitroglycerin (NTG) delivery systems in the form of patches were developed for controlled administration of nitroglycerin. These patches overcome the inherent problems of the ointment i.e., accuracy of dose, application, and staining. In addition, they release nitroglycerin at a uniform rate over a 24 hour period.
Belgian Pat. No. 893,394 describes a membrane-controlled delivery system for NTG. Materials and manufacturing for this device are complicated and costly. U.S. Pat. Nos. 4,336,243 and 4,291,015 describe matrix-controlled delivery systems. These are both bulky and inefficient requiring a wide perimeter of adhesive to insure intimate skin contact.
In addition, all three patches require a large excess of NTG to maintain a driving force for penetration.
Goodhart, et al., J Pharm. Sci. 65, No. 10, 1466 (1976) described the stabilization of compressed NTG tablets with polyvinylpyrrolidone (PVP). It was observed that the volatility and subsequent migration of the NTG was retarded with addition of PVP. European Pat. No. 054,279 describes the use of water-insoluble PVP cross-linked or copolymerized with acrylic or vinyl esters to provide a hydrophobic matrix system for controlled release of NTG. This matrix also reduces the drug's volatility. The present invention relates to the use of a nitroglycerin water soluble polyvinylpyrrolidone complex as both film-former and rate-controlling mechanism for the transdermal delivery of NTG.